Quaternization solvent effects

Solvent effects also depend on the ground-state structure of the substrate and on the transition-state structure, as is shown below. Here let us merely note that A-heterocyclic compounds tend to form a hydrogen bond with hydroxylic solvents even in the ground state. Hydrogen-bond formation in this case is a change in the direction of quaternization of the aza group, as demonstrated by spectral evidence. Therefore, it is undoubtedly a rate-enhancing interaction. 

Solvent effects on relative rate constants are also usually small. When a heteroaromatic compound quaternizes at more than one site, for example, the product ratio can be insensitive to solvent variations. A constant isomer ratio is recorded for methylation (Mel) of 3-/erf-butyl-6-dimethylaminopyridazine (10), in hexane, benzene, carbon tetrachloride, acetone, and acetonitrile, but not in dimethoxyethane or tetrahydrofuran. The suggestion was made that Mel may have reacted with the last two ether solvents to give an oxonium ion. Since the identity of the quaternizing agent changes, the product ratio varies as well.13... 

The role of solvent effects in quaternization is one of the first physical organic studies and this is due to Menschutkin (1879LA334). It shows an increase in relative rate from 1 to 742 on going from benzene to benzyl alcohol, which suggests no simple explanation. Typical ranges of solvent-dependent rate ratios are 15,700/1 (nitromethane/cyclohexane) in the alkylation of triethylamine by methyl iodide (68BSF2678), 1660/1 [dimethylsulfoxide (DMSO)/carbon tetrachloride] in the reaction of l,4-diazabicyclo[2,2,2]-octane (DABCO) (5) with (2-bromoethyl)benzene (75JA7433) (Scheme 5),... 

Quaternary salts, isolation of, 10 Quaternization, by alkyl halides, 2-7 by aryl halides, 7-9 on carbon, 53 definition of, 2 by dimethyl sulfate, 9 electronic effects in, 11 in JV-heterocycles, 16, 38 by heterocyclyl halides, 7—9 isotope effect on, 55 mechanism of, 53-56 by methyl euyl-sulfonates, 9, 10 on oxygen, 52 rates of, 55 reagents for, 2-10 by self-condensation, 8 solvent effect on, 10, 55 solvents for, 10 steric effects on, 12, 13 substituents, influence on, 11, 19, 23 on sulfur, 51 Quinaldine, 4-amino-, 4 Quinazolines, 2-alkyl-, salt formation of, 6... 

Despite the greater acidities of the diazoles and triazoles (pKa = 10-14), fairly vigorous reaction conditions are still required for the alkylation of the unsubstituted systems [26] (Table 5.32) and the effectiveness of the alkylation of pyrazoles and imidazoles is enhanced under solidiliquid conditions [27-30]. Under these conditions, quaternization is avoided if no solvent is added [27],... 

Bearing in mind that chemical shifts are usually not dependent on the solvent or concentration, but may be partly dependent on the anion37, quaternization of alkyl-phosphines causes an upfield shift (1-7 ppm) for the near carbons of the alkyl chain, the effect becoming only slightly detectable on C(y) carbons37,94. Where triarylphosphines are quaternized, the chemical shift of the phenyl ipso carbon Cf moves upfield whereas that of the Cpara carbon moves downfield, as expected from the polarization of the 71-electron density in the phenyl ring36,37. For the aromatic carbon atoms, the increments... 

The quantitative effects of -substituents in decreasing the rates of these reactions are not additive and also depend considerably on solvent and alkylating agent. They are low in liquid sulfur dioxide as a solvent where solvation effects are small and the high dielectric constant increases the bond breaking in the transition state. For 3- and 4-substituted pyridines a Br nsted correlation exists between the rates of quaternization and the pKa values <1978AFIG(22)71 >. 

The more conventional ionic liquids are generally prepared in a two-step procedure from the corresponding amine or phosphine (Figure 6.2). Alkylation leads to quaternization of the heteroatom and then anion metathesis can be performed if desired. The most effective way to perform the quaternization is in solvent free conditions under microwave irradiation. As they need to be prepared, RTILs are less green than many other alternative solvents in terms of life cycle... 

Uses. Tetramethylene sulfone has high solvent power for aromatics and has been used extensively by Olah and co-workers for Friedel-Crafts type nitrations and for studies of the mechanism of nitronium tetrafluoroborate nitration of alkyl-benzenes and halobenzenes in homogeneous solution. It is a superior solvent for quaternization of tertiary amines with alkyl halides, since it has a high dielectric constant and does not enter into side reactions observed with nitrobenzene and dimethylformamide. For example in the synthesis of the acridizinium salt (3), Bradsher and Parham effected quaternization of (1) with benzyl bromide in tetramethylene sulfone at room temperature in excellent yield. Several other salts analagous to (2) were obtained in good yield and in crystalline form with use of tetramethylene sulfone, whereas with other solvents the products were colored... 

Curiously, when liquid sulfur dioxide is used as a solvent and Mel as the quaternizing agent, one ortho methyl group retards the rate by 1% and the second by 44%. Although nonadditivity is observed, these kinetic effects are surprisingly small. 

The reaction rates for quaternization of pyridazines provide a measure of the steric effect of alkyl groups.269 Rates for 3,6-dialkylpyridazines with methyl iodide show that the product distribution is kinetically controlled and is solvent dependent. Moreover, steric effects of substituents prevail... 

Figure 3. Effect of solvent on the reduced viscosity-concentration plots for a,cu -quaternary ammonium chloride-PMS at 25 C ( ) toluene, (A) THF, ( ) DMF and ( ) non-quaternized a,w -di tert-amino PMS in DMF.

Yellow colour appears immediately after mixing of the two reagents which fades out progressively as the reaction proceeds. This colour is due to the absorption of a n—n type CT complex amine-anhydride of composition 1 1. The reactions have been carried out in a series of moisture-free aprotic solvents possessing general and specific effects. A typical exemple is given by the quaternization of trie thy lamine with tetra-chlorophthalic anhydride (Table II). 

In a systemic kinetic study of the reaction of various amines with chloromethylated polystyrene (CMPS), Kawabe and coworkers found the rate profiles to be significantly Influenced by the nature of amine and the reaction media They observed that some cases conformed to simple second order reaction rate laws, but slight variations in the reaction conditions produced either deceleration or acceleration as quaternization proceeded (Table I) The deceleration was observed in the reactions of bulky amines i.e., diethyl-amine or dibutylamine, in DMF, DMSO and dioxane. This rate retardation could be attributed to the steric hindrance imposed by the quaternized neighboring group. The nature of the solvent also played an important role in the quaternization process for instance, a normal second order reaction was observed between triethylamine and CMPS in DMF. In DMSO, a deceleration attributed to an electrostatic effect was observed. ... 

The initial velocity of quinuclidine substitution is significantly faster than that of triethylamine at the same temperature (Table III, runs 21-23), even though the former was investigated in a mixed solvent. Similar results were found in the quaternization of the model compound. If a steric effect were considered to be the sole factor producing the decrease in k with respect to kQ, one would expect that (1) hQ/k2 for quinuclidine substitution should be smaller than hQ/k2 for TEA substitution and/or (2) the initial linearity in the second order plot would extend beyond 52% conversion where deviation occurs in the triethylamine system. Experimental results refute these expectations rate retardation is enhanced in quinuclidine reactions, furtherfore, the break point is almost the same for both cases. 

If the flexibility of the polymer chain is reduced, the tendency to fold in to domains must decrease. Each charge must be localized within the polymer backbone, which is a low dielectric region. Solvation of individual counterions will become the primary mode of product stabilization. If the counterions are tightly bound to individual groups, the solvent molecules must be highly ordered to effect solvation. Further, the extent of solvation will have a pronounced impact upon the stability of the transition state, and the reaction rate will be very sensitive to solvent variations. We have noted that DMSO is very difficult to remove quantitatively from quaternized polymers and that the polyquats are extremely hydroscopic. These observations indicate that solvent molecules are very strongly bound to the ionic sites. 

In general, polar solvents speed up the quaternization reaction322-4 . To some extent the effect of solvents follows their dipole moments322 but the connection is not general, and with solvents of high polarity (tetramethylene sulphone, D = 42 propylene carbonate, D = 65 1) examples are known of quaternizations which are faster in the less polar medium3246. The reaction of pyridine with alkyl halides has been used to elucidate the ways in which the parameters of the Arrhenius equation vary with changes in solvent 323, 324, 325 YoT preparative purposes alcohol is often used as the solvent, but for slow reactions nitrobenzene is useful. 

The quaternization of pyridine in non-polar solvents has been studied as a means of clarifying the much debated nature of the displacement reaction under such circumstances . Swain and Eddy i deduced evidence for their theory of specific solvation from the reaction of pyridine and methyl bromide in benzene containing various hydroxylic solutes. Swain and Langs-dorf45ii> found the Hammett plot for the reaction of substituted benzyl bromides with pyridine in acetone to be markedly concave, and indeed to fall into two separate lines for meta- and / zm-substituents. The curvature and the division illustrate the effects of substituents upon reactions of intermediate character. Ingold and his co-workers from reactions in sulphur dioxide,... 

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